Differential effects of diet-induced dyslipidemia and hyperglycemia on mesenteric resistance artery structure and function in type 2 diabetes.
Type 2 diabetes and dyslipidemia oftentimes present in combination. However, the relative roles of diabetes and diet-induced dyslipidemia in mediating changes in vascular structure, mechanics, and function are poorly understood. Our hypothesis was that addition of a high-fat diet would exacerbate small artery remodeling, compliance, and vascular dysfunction in type 2 diabetes. Vascular remodeling indices [media/lumen (M/L) ratio, collagen abundance and turnover, and matrix metalloproteinase dynamics], mechanical properties (vessel stiffness), and reactivity to pressure and vasoactive factors were measured in third-order mesenteric arteries in control Wistar and type 2 diabetic Goto-Kakizaki (GK) rats fed either a regular or high-fat diet. M/L ratios, total collagen, and myogenic tone were increased in diabetes. Addition of the high-fat diet altered collagen patterns (mature versus new collagen) in favor of matrix accumulation. Addition of a high-fat diet caused increased constriction to endothelin-1 (0.1-100 nM), showed impaired vasorelaxation to both acetylcholine (0.1 nM-1 microM) and sodium nitroprusside (0.1 nM-1 microM), and increased cardiovascular risk factors in diabetes. These results suggest that moderate elevations in blood glucose, as seen in our lean GK model of type 2 diabetes, promote resistance artery remodeling resulting in increased medial thickness, whereas addition of a high-fat diet contributes to diabetic vascular disease predominantly by impairing vascular reactivity in the time frame used for this study. Although differential in their vascular effects, both hyperglycemia and diet-induced dyslipidemia need to be targeted for effective prevention and treatment of diabetic vascular disease.
Sachidanandam
Kamakshi
K
Program in Clinical and Experimental Therapeutics, College of Pharmacy, University of Georgia, Augusta, Georgia, USA.
Hutchinson
Jim R
JR
Elgebaly
Mostafa M
MM
Mezzetti
Erin M
EM
Wang
Mong-Heng
MH
Ergul
Adviye
A
D000109:Acetylcholine / Q000494:pharmacology; D000792:Angiography; D000818:Animals; D003094:Collagen / Q000378:metabolism; D003924:Diabetes Mellitus, Type 2 / Q000453:epidemiology* / Q000503:physiopathology*; D003925:Diabetic Angiopathies / Q000139:chemically induced / Q000503:physiopathology / Q000517:prevention & control; D004041:Dietary Fats / Q000009:adverse effects*; D004195:Disease Models, Animal; D050171:Dyslipidemias / Q000150:complications* / Q000503:physiopathology*; D006801:Humans; D006943:Hyperglycemia / Q000150:complications* / Q000503:physiopathology*; D008297:Male; D020782:Matrix Metalloproteinases / Q000378:metabolism; D008638:Mesenteric Arteries / Q000502:physiology* / Q000503:physiopathology; D009599:Nitroprusside / Q000494:pharmacology; D051381:Rats; D017208:Rats, Wistar; D012307:Risk Factors; D014655:Vascular Resistance / Q000502:physiology*; D014661:Vasoconstriction; D014664:Vasodilation / Q000187:drug effects
D004041:Dietary Fats; D009599:Nitroprusside; D003094:Collagen; D020782:Matrix Metalloproteinases; D000109:Acetylcholine